Notch1 signaling in pyramidal neurons regulates synaptic connectivity and experience-dependent modifications of acuity in the visual cortex.
How the visual cortex responds to specific stimuli is strongly influenced by visual experience during development. Monocular deprivation, for example, changes the likelihood of neurons in the visual cortex to respond to input from the deprived eye and reduces its visual acuity. Because these functional changes are accompanied by extensive reorganization of neurite morphology and dendritic spine turnover, genes regulating neuronal morphology are likely to be involved in visual plasticity. In recent years, Notch1 has been shown to mediate contact inhibition of neurite outgrowth in postmitotic neurons and implicated in the pathogenesis of various degenerative diseases of the CNS. Here, we provide the first evidence for the involvement of neuronal Notch1 signaling in synaptic morphology and plasticity in the visual cortex. By making use of the Cre/Lox system, we expressed an active form of Notch1 in cortical pyramidal neurons several weeks after birth. We show that neuronal Notch1 signals reduce dendritic spine and filopodia densities in a cell-autonomous manner and limit long-term potentiation in the visual cortex. After monocular deprivation, these effects of Notch1 activity predominantly affect responses to visual stimuli with higher spatial frequencies. This results in an enhanced effect of monocular deprivation on visual acuity.
Dahlhaus
Martijn
M
Department of Molecular Visual Plasticity, Netherlands Institute for Neuroscience, Institute of the Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands.
Hermans
Josephine M
JM
Van Woerden
Leonard H
LH
Saiepour
M Hadi
MH
Nakazawa
Kazu
K
Mansvelder
Huibert D
HD
Heimel
J Alexander
JA
Levelt
Christiaan N
CN
D000818:Animals; D000831:Animals, Newborn; D049229:Dendritic Spines / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology; D007839:Functional Laterality; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D010775:Photic Stimulation / Q000379:methods; D011554:Pseudopodia / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology* / Q000648:ultrastructure; D051881:Receptor, Notch1 / Q000235:genetics / Q000502:physiology*; D012683:Sensory Deprivation; D015398:Signal Transduction / Q000502:physiology*; D016622:Silver Staining / Q000379:methods; D013569:Synapses / Q000502:physiology*; D015349:Vision, Monocular / Q000502:physiology; D014792:Visual Acuity / Q000235:genetics; D014793:Visual Cortex / Q000166:cytology* / Q000254:growth & development
D051881:Receptor, Notch1; D049452:Green Fluorescent Proteins